Authors: | Stur, E.; Peng, F.; Teng, P. N.; Bayraktar, E.; Hu, M.; Corvigno, S.; Brown, D. J.; Lee, S.; Moore, K. N.; Bateman, N. W.; Darcy, K. M.; Maxwell, G. L.; Conrads, T. P.; Sahni, N.; Vázquez-García, I.; Shah, S. P.; Celestino, J.; Fleming, N. D.; Navin, N. E.; Wang, L.; Sood, A. K. |
Article Title: | The dynamic immune behavior of primary and metastatic ovarian carcinoma |
Abstract: | Patients with high-grade serous ovarian carcinoma (HGSC) are usually diagnosed with advanced-stage disease, and the tumors often have immunosuppressive characteristics. Together, these factors are important for disease progression, drug resistance, and mortality. In this study, we used a combination of single-cell sequencing and spatial transcriptomics to identify the molecular mechanisms that lead to immunosuppression in HGSC. Primary tumors consistently showed a more active immune microenvironment than did omental tumors. In addition, we found that untreated primary tumors were mostly populated by dysfunctional CD4 and CD8 T cells in later stages of differentiation; this, in turn, was correlated with expression changes in the interferon α and γ pathways in epithelial cells, showing that cross-communication between the epithelial and immune compartments is important for immune suppression in HGSC. These findings could have implications for the design of clinical trials with immune-modulating drugs. © The Author(s) 2025. |
Keywords: | adult; clinical article; controlled study; human tissue; protein expression; aged; middle aged; survival analysis; cancer surgery; primary tumor; overall survival; cancer combination chemotherapy; alpha interferon; paclitaxel; cancer staging; flow cytometry; cd8 antigen; cd8+ t lymphocyte; cell function; carboplatin; quality of life; transcriptomics; cell heterogeneity; alpha smooth muscle actin; lymphocyte differentiation; immune response; gamma interferon; cd4+ t lymphocyte; ovary carcinoma; reactive oxygen metabolite; epithelium cell; ovary metastasis; cd4 antigen; neoadjuvant chemotherapy; peritoneum metastasis; fluorescence activated cell sorting; transcriptome; oxidative phosphorylation; hla antigen; immunocompetent cell; hla system; memory t lymphocyte; tumor microenvironment; copy number variation; spatial analysis; dimensionality reduction; human; female; article; differential gene expression; gene set enrichment analysis; single cell rna seq |
Journal Title: | npj Precision Oncology |
Volume: | 9 |
ISSN: | 2397-768X |
Publisher: | Springer Nature |
Date Published: | 2025-04-25 |
Start Page: | 120 |
Language: | English |
DOI: | 10.1038/s41698-025-00818-8 |
PROVIDER: | scopus |
PMCID: | PMC12032089 |
PUBMED: | 40281242 |
DOI/URL: | |
Notes: | Article -- Source: Scopus |